Nicotine DependencePhase 2NCT04696380
Do Flavors Increase the Addiction Potential of Nicotine?
A Phase 2 study testing Nicotine and JUUL e-cigarette in people with Nicotine Dependence, run by University of Vermont at 1 site in United States.
Trial summary
The FDA has concluded that flavors (e.g. menthol) are associated with greater addiction potential in tobacco cigarettes (Gottlieb March 13, 2019). Whether the same is true for e-cigarettes and non-menthol flavors is unclear and our study should help answer this question. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence
- What is being tested?
- Nicotine and JUUL e-cigarette
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2021to 31 Aug 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 21 years or older
- comfortable reading and writing English
- own a JUUL brand e-cigarette they have used at least 10 times in the past 30 days
- use JUUL e-cigarettes and JUUL pods with 5% nicotine
- used e-cigarettes on 4+ days a week in the last 30 days
- use or do not use tobacco cigarettes
Show all 10Show fewer
- do not plan to quit e-cigarettes in the next 30 days
- non-pregnant females verified by pregnancy test
- access to the internet in a location where they could join a videoconference call and legally use their JUUL.
- Reside in VT
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Do Flavors Increase the Addiction Potential of Nicotine?: A Pilot Laboratory Study
The FDA has concluded that flavors (e.g. menthol) are associated with greater addiction potential in tobacco cigarettes (Gottlieb March 13, 2019). Whether the same is true for e-cigarettes and non-menthol flavors is unclear and our study should help answer this question.
Our major hypothesis is that the pharmacological effect of nicotine to induce addiction will be greater with use of a preferred e-cigarette flavor than with use of a non-preferred flavor. The pharmacological effect will be measured by how much a larger nicotine dose increases addiction potential compared to a smaller dose.
Read the detailed description
Study Design:
Fifteen participants who currently use e-cigarettes weekly and who use or do not use tobacco cigarettes will enter a remote session study. Participants will be asked to abstain from all nicotine/tobacco products, non-nicotine electronic cigarettes, and THC containing products for 16 hours prior to four experimental sessions and will be tested in a 2x2 within-participants design with four conditions: 1) low nicotine dose (3%)/non-preferred flavor, 2) low dose/preferred flavor, 3) high dose (5%)/non-preferred flavor, and 4) high dose/preferred flavor. Order of testing will be randomized. Participants and experimenters will be blind to dose. The major outcomes will be subjective effects, e.g. liking and tests of reinforcement (choice procedures). We will require 16 hours of abstinence prior to each remote experimental session to increase the sensitivity to nicotine effects.
The consent process, experimental sessions and data collection will all be done remotely using a secure video platform. The only interaction between participants and research staff will be the curbside pick-up of study products, which will follow social distancing and mask guidelines. Participants will pick up study JUUL pods curb-side at the University of Vermont before their baseline videoconference session. Participants will be required to conduct all videoconference sessions in a place where they can legally use their JUUL.
The consent videoconference session will be conducted prior to the baseline and four experimental sessions. Participants will be assessed for COVID-19 and E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) symptoms prior to the curbside pick-up and at the start of the 5 videoconference sessions in which they will be asked to vape. During the baseline session, participants will complete a baseline questionnaire via online survey and then answer a series of questions about nicotine dependence and how many JUUL pods they would purchase at varying prices. Participants will then sample the two flavors available for JUUL -Virginia Tobacco and Menthol- using their own JUUL device. Research staff will ask participants to rate the pleasantness of each flavor and, after they have tried the flavors, participants will rank order their flavor preferences to determine their preferred flavor of the two. Finally, participants will be trained in the puffing protocol to be used in the experimental sessions.
During each experimental videoconference session, participants will report on their recent e-cigarette and tobacco product use at the start of each videoconference testing session. Those reporting non-abstinence will have their videoconference session rescheduled. During the videoconference testing sessions participants will be asked to puff either tobacco flavor 3% nicotine, tobacco flavor 5% nicotine, menthol flavor 3% nicotine, or menthol flavor 5% nicotine. After each puffing bout within each session, they will answer questions about about e-cigarette effects, e-cigarette liking and wanting, like/dislike of e-cigarette taste and e-cigarette intensity. At the end of each session, they will be asked how many JUUL pods they would purchase at varying prices.
Adverse events will be collected at the end of each videoconference session by the research assistant, who will consult with the study licensed medical provider.
- Conditions
- Nicotine Dependence
- Being tested
- Nicotine, JUUL e-cigarette
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicotineDrug
Participants will sample high vs low nicotine.
JUUL e-cigaretteDevice
Participants will sample preferred vs non-preferred JUUL flavors.
| Study group | Role | What they receive |
|---|---|---|
| High nicotine, preferred flavor | Experimental | Participants will sample their preferred flavored JUUL e-cigarette at 5% nicotine strength. Receives: Drug: Nicotine; Device: JUUL e-cigarette |
| High nicotine, non-preferred flavor | Experimental | Participants will sample their non-preferred flavored JUUL e-cigarette at 5% nicotine strength. Receives: Drug: Nicotine; Device: JUUL e-cigarette |
| Low nicotine, preferred flavor | Experimental | Participants will sample their preferred flavored JUUL e-cigarette at 3% nicotine strength. Receives: Drug: Nicotine; Device: JUUL e-cigarette |
| Low nicotine, non-preferred flavor | Experimental | Participants will sample their non-preferred flavored JUUL e-cigarette at 3% nicotine strength. Receives: Drug: Nicotine; Device: JUUL e-cigarette |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liking and wanting nicotine
Average of "I feel good e-cigarette effects", "I want more of that e-cigarette I received", "I feel the e-cigarette strength" and "I like the e-cigarette effect" on a 0-100mm scale from "not at all" (0) to "extremely" (100).
Measured: 2 weeks
E-cigarette purchase task
This is a modification of the Cigarette Purchase Task that asks how much users would spend to obtain their usual amount of e-liquids to use.
Measured: 2 weeks
E-cigarette and tobacco cigarette craving
Modified items from the Mood and Physical Symptoms Scale that asks about change/strength of urges for e-cigarettes and tobacco cigarettes (0-4 scale, 0= not at all and 4= extremely) and strength of urges (1-5 scale, 1=slight and 5= extremely strong).
Measured: 2 weeks
Modified Drug Effect Questionnaire
Modified version of the Drug Effects Questionnaire where participants rate acute responses to the e-cigarette drug effects on a 0-100 mm scale, from "not at all" (0) to "extremely" (100).
Measured: 2 weeks
Modified Labeled Hedonic Scale
1 item about like/dislike of the e-cigarette taste using a modified version of the Labeled Hedonic Scale, a category ratio scale that ranges from -100 (most disliked) to 100 (most liked).
Measured: 2 weeks
Modified Labeled Magnitude Scale
1 item about e-cigarette taste intensity using a modified version of the Labeled Magnitude Scale, which is a category ratio scale with 7 semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", with responses coded on a 0-100 scale (0= no sensation, 100= strongest imaginable).
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2021
- Study start1 Mar 2021
- Primary completion31 Aug 2021
- Study completion31 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nicotine DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Hughes, MD, University of Vermont
- Investigators
- John R Hughes, MD, Principal investigator, University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04696380
- Sponsor's protocol ID
- CHRMS 00000555
- Status last verified
- Mar 2022
- First submitted
- 23 Nov 2020
- Last updated
- 22 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Peasley-Miklus C, Klemperer EM, Hughes JR, Villanti AC, Krishnan-Sarin S, DeSarno MJ, Mosca LA, Su A, Cassidy RN, Feinstein MJP. The interactive effects of JUUL flavor and nicotine concentration on addiction potential. Exp Clin Psychopharmacol. 2023 Apr;31(2):336-342. doi: 10.1037/pha0000591. Epub 2022 Sep 1.
PubMed 36048114
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Flavors Increase the Addiction Potential of Nicotine?: A Pilot Laboratory Study
- ClinicalTrials.gov ID
- NCT04696380
- Acronym / sponsor ID
- CHRMS 00000555
- Conditions
- Nicotine Dependence
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 31 Aug 2021 (actual)
- Study completion
- 31 Aug 2021 (actual)
- First posted
- 6 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The FDA has concluded that flavors (e.g. menthol) are associated with greater addiction potential in tobacco cigarettes (Gottlieb March 13, 2019). Whether the same is true for e-cigarettes and non-menthol flavors is unclear and our study should help answer this question.
Our major hypothesis is that the pharmacological effect of nicotine to induce addiction will be greater with use of a preferred e-cigarette flavor than with use of a non-preferred flavor. The pharmacological effect will be measured by how much a larger nicotine dose increases addiction potential compared to a smaller dose.
Detailed description
Study Design:
Fifteen participants who currently use e-cigarettes weekly and who use or do not use tobacco cigarettes will enter a remote session study. Participants will be asked to abstain from all nicotine/tobacco products, non-nicotine electronic cigarettes, and THC containing products for 16 hours prior to four experimental sessions and will be tested in a 2x2 within-participants design with four conditions: 1) low nicotine dose (3%)/non-preferred flavor, 2) low dose/preferred flavor, 3) high dose (5%)/non-preferred flavor, and 4) high dose/preferred flavor. Order of testing will be randomized. Participants and experimenters will be blind to dose. The major outcomes will be subjective effects, e.g. liking and tests of reinforcement (choice procedures). We will require 16 hours of abstinence prior to each remote experimental session to increase the sensitivity to nicotine effects.
The consent process, experimental sessions and data collection will all be done remotely using a secure video platform. The only interaction between participants and research staff will be the curbside pick-up of study products, which will follow social distancing and mask guidelines. Participants will pick up study JUUL pods curb-side at the University of Vermont before their baseline videoconference session. Participants will be required to conduct all videoconference sessions in a place where they can legally use their JUUL.
The consent videoconference session will be conducted prior to the baseline and four experimental sessions. Participants will be assessed for COVID-19 and E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) symptoms prior to the curbside pick-up and at the start of the 5 videoconference sessions in which they will be asked to vape. During the baseline session, participants will complete a baseline questionnaire via online survey and then answer a series of questions about nicotine dependence and how many JUUL pods they would purchase at varying prices. Participants will then sample the two flavors available for JUUL -Virginia Tobacco and Menthol- using their own JUUL device. Research staff will ask participants to rate the pleasantness of each flavor and, after they have tried the flavors, participants will rank order their flavor preferences to determine their preferred flavor of the two. Finally, participants will be trained in the puffing protocol to be used in the experimental sessions.
During each experimental videoconference session, participants will report on their recent e-cigarette and tobacco product use at the start of each videoconference testing session. Those reporting non-abstinence will have their videoconference session rescheduled. During the videoconference testing sessions participants will be asked to puff either tobacco flavor 3% nicotine, tobacco flavor 5% nicotine, menthol flavor 3% nicotine, or menthol flavor 5% nicotine. After each puffing bout within each session, they will answer questions about about e-cigarette effects, e-cigarette liking and wanting, like/dislike of e-cigarette taste and e-cigarette intensity. At the end of each session, they will be asked how many JUUL pods they would purchase at varying prices.
Adverse events will be collected at the end of each videoconference session by the research assistant, who will consult with the study licensed medical provider.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| High nicotine, preferred flavor | Experimental | Drug: Nicotine, Device: JUUL e-cigaretteParticipants will sample their preferred flavored JUUL e-cigarette at 5% nicotine strength. |
| High nicotine, non-preferred flavor | Experimental | Drug: Nicotine, Device: JUUL e-cigaretteParticipants will sample their non-preferred flavored JUUL e-cigarette at 5% nicotine strength. |
| Low nicotine, preferred flavor | Experimental | Drug: Nicotine, Device: JUUL e-cigaretteParticipants will sample their preferred flavored JUUL e-cigarette at 3% nicotine strength. |
| Low nicotine, non-preferred flavor | Experimental | Drug: Nicotine, Device: JUUL e-cigaretteParticipants will sample their non-preferred flavored JUUL e-cigarette at 3% nicotine strength. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 21 years or older
- comfortable reading and writing English
- own a JUUL brand e-cigarette they have used at least 10 times in the past 30 days
- use JUUL e-cigarettes and JUUL pods with 5% nicotine
- used e-cigarettes on 4+ days a week in the last 30 days
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NicotineParticipants will sample high vs low nicotine. | Drug | High nicotine, non-preferred flavor, High nicotine, preferred flavor, Low nicotine, non-preferred flavor, Low nicotine, preferred flavor |
| JUUL e-cigaretteParticipants will sample preferred vs non-preferred JUUL flavors. | Device | High nicotine, non-preferred flavor, High nicotine, preferred flavor, Low nicotine, non-preferred flavor, Low nicotine, preferred flavor |
Primary outcome
Liking and wanting nicotine
Time frame: 2 weeks
Average of "I feel good e-cigarette effects", "I want more of that e-cigarette I received", "I feel the e-cigarette strength" and "I like the e-cigarette effect" on a 0-100mm scale from "not at all" (0) to "extremely" (100).
E-cigarette purchase task
Time frame: 2 weeks
This is a modification of the Cigarette Purchase Task that asks how much users would spend to obtain their usual amount of e-liquids to use.
E-cigarette and tobacco cigarette craving
Time frame: 2 weeks
Modified items from the Mood and Physical Symptoms Scale that asks about change/strength of urges for e-cigarettes and tobacco cigarettes (0-4 scale, 0= not at all and 4= extremely) and strength of urges (1-5 scale, 1=slight and 5= extremely strong).
Modified Drug Effect Questionnaire
Time frame: 2 weeks
Modified version of the Drug Effects Questionnaire where participants rate acute responses to the e-cigarette drug effects on a 0-100 mm scale, from "not at all" (0) to "extremely" (100).
Modified Labeled Hedonic Scale
Time frame: 2 weeks
1 item about like/dislike of the e-cigarette taste using a modified version of the Labeled Hedonic Scale, a category ratio scale that ranges from -100 (most disliked) to 100 (most liked).
Modified Labeled Magnitude Scale
Time frame: 2 weeks
1 item about e-cigarette taste intensity using a modified version of the Labeled Magnitude Scale, which is a category ratio scale with 7 semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", with responses coded on a 0-100 scale (0= no sensation, 100= strongest imaginable).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2022.
- Derived from this study: PubMed 36048114Peasley-Miklus C, Klemperer EM, Hughes JR, Villanti AC, Krishnan-Sarin S, DeSarno MJ, Mosca LA, Su A, Cassidy RN, Feinstein MJP. The interactive effects of JUUL flavor and nicotine concentration on addiction potential. Exp Clin Psychopharmacol. 2023 Apr;31(2):336-342. doi: 10.1037/pha0000591. Epub 2022 Sep 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John R Hughes, MD principal investigator
University of Vermont
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotine and JUUL e-cigarette in people with Nicotine Dependence, run by University of Vermont at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liking and wanting nicotine (time frame: 2 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04696380, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2022.